Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGK6ANL)

• DOT Name: Fibroblast growth factor 7 (FGF7)
• Synonyms: FGF-7; Heparin-binding growth factor 7; HBGF-7; Keratinocyte growth factor
• Gene Name: FGF7
• UniProt ID: FGF7_HUMAN
• Pfam ID: PF00167
• Sequence:
  MHKWILTWILPTLLYRSCFHIICLVGTISLACNDMTPEQMATNVNCSSPERHTRSYDYME
  GGDIRVRRLFCRTQWYLRIDKRGKVKGTQEMKNNYNIMEIRTVAVGIVAIKGVESEFYLA
  MNKEGKLYAKKECNEDCNFKELILENHYNTYASAKWTHNGGEMFVALNQKGIPVRGKKTK
  KEQKTAHFLPMAIT
• Function: Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. Growth factor active on keratinocytes. Possible major paracrine effector of normal epithelial cell proliferation.
• Tissue Specificity: Epithelial cell.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  (FGFR2)
  PIP3 activates AKT signaling (R-HSA-1257604)
  FGFR2b ligand binding and activation (R-HSA-190377)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Fibroblast growth factor 7 (FGF7) decreases the response to substance of Hydrogen peroxide.	[15]
Fluorouracil	DMUM7HZ	Approved	Fibroblast growth factor 7 (FGF7) decreases the response to substance of Fluorouracil.	[16]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fibroblast growth factor 7 (FGF7).	[1]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Fibroblast growth factor 7 (FGF7).	[12]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibroblast growth factor 7 (FGF7).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibroblast growth factor 7 (FGF7).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Fibroblast growth factor 7 (FGF7).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fibroblast growth factor 7 (FGF7).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Fibroblast growth factor 7 (FGF7).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Fibroblast growth factor 7 (FGF7).	[7]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Fibroblast growth factor 7 (FGF7).	[6]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Fibroblast growth factor 7 (FGF7).	[8]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Fibroblast growth factor 7 (FGF7).	[9]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Fibroblast growth factor 7 (FGF7).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fibroblast growth factor 7 (FGF7).	[11]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Fibroblast growth factor 7 (FGF7).	[13]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Suramin	DMTOUY9	Investigative	Suramin affects the localization of Fibroblast growth factor 7 (FGF7).	[14]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Regulation of keratinocyte growth factor and scatter factor in cyclosporin-induced gingival overgrowth. J Oral Pathol Med. 2004 Aug;33(7):391-7. doi: 10.1111/j.1600-0714.2004.00223.x.
• [3] Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21737-42. doi: 10.1073/pnas.1007863107. Epub 2010 Nov 22.
• [4] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [7] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [8] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [9] Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab. 2005 Feb;90(2):936-43.
• [10] Keratinocyte growth factor is upregulated by the hyperplasia-inducing drug nifedipine. Cytokine. 2000 Oct;12(10):1566-9. doi: 10.1006/cyto.2000.0756.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [14] Keratinocyte growth factor-1 expression in healthy and diseased human periodontal tissues. J Periodontal Res. 2005 Apr;40(2):118-28. doi: 10.1111/j.1600-0765.2004.00780.x.
• [15] KGF prevents oxygen-mediated damage in ARPE-19 cells. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3435-42. doi: 10.1167/iovs.04-1487.
• [16] Silencing of keratinocyte growth factor receptor restores 5-fluorouracil and tamoxifen efficacy on responsive cancer cells. PLoS One. 2008 Jun 25;3(6):e2528. doi: 10.1371/journal.pone.0002528.